Methanesulfonyl chloride → benzhydryl 1-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[[(2R,3S)-2-[[4-(methylsulfonyloxymethyl)triazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

HRID 708493Notes

Reaction equation

HRID 708493 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12](/[C:14](=[N:31]/[O:32][C:33]2([C:36]([O:38][CH:39]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[O:37])[CH2:35][CH2:34]2)/[C:15]([NH:17][C@@H:18]2[C:21](=[O:22])[NH:20][C@@H:19]2[CH2:23][N:24]2[N:28]=[C:27]([CH2:29][OH:30])[CH:26]=[N:25]2)=[O:16])[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[CH3:61][S:62](Cl)(=[O:64])=[O:63]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C:9]1[S:10][CH:11]=[C:12](/[C:14](=[N:31]/[O:32][C:33]2([C:36]([O:38][CH:39]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)=[O:37])[CH2:34][CH2:35]2)/[C:15]([NH:17][C@@H:18]2[C:21](=[O:22])[NH:20][C@@H:19]2[CH2:23][N:24]2[N:28]=[C:27]([CH2:29][O:30][S:62]([CH3:61])(=[O:64])=[O:63])[CH:26]=[N:25]2)=[O:16])[N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 118379587benzhydryl 1-[(Z)-[2-[[(2R,3S)-2-[[4-(hydroxymethyl)triazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylate

Product 1

HCID 118379964benzhydryl 1-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[[(2R,3S)-2-[[4-(methylsulfonyloxymethyl)triazol-2-yl]methyl]-4-oxoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxycyclopropane-1-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of benzhydryl 1-(((Z)-(1-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)-2-(((2R,3S)-2-((4-(hydroxymethyl)-2H-1,2,3-triazol-2-yl)methyl)-4-oxoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)cyclopropanecarboxylate (178 mg, 0.25 mmol) and DIPEA (65 μL, 0.37 mmol) in DCM (2.5 mL) at 0° C. was added MsCl (25 μL, 0.32 mmol). After 1 h at 0° C., the reaction mixture was diluted with DCM (10 mL), washed with 0.2 N HCl and saturated NaHCO3 (aq). The organic layer was dried over Na2SO4, concentrated in vacuo to afford the title compound (190 mg, 96%). The crude residue was used as such in the following step. LCMS: Rt=1.05 min, m/z=795.4 (M+1) Method 2m_acidic.

Workup

  1. washwashed with 0.2 N HCl and saturated NaHCO3 (aq)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96427472000e4d4f8d79cc60d966d709
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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